|Year : 2014 | Volume
| Issue : 3 | Page : 304-309
Clinical and microbiological characteristics of Rhodotorula mucilaginosa infections in a tertiary-Care facility
MR Capoor1, S Aggarwal1, C Raghvan2, DK Gupta3, AK Jain2, R Chaudhary2
1 Department of Microbiology, Vardhman Mahaveer Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Neurology, Vardhman Mahaveer Medical College and Safdarjung Hospital, New Delhi, India
3 Department of Hematology, Vardhman Mahaveer Medical College and Safdarjung Hospital, New Delhi, India
|Date of Submission||02-Jun-2013|
|Date of Acceptance||02-Jan-2014|
|Date of Web Publication||10-Jul-2014|
M R Capoor
Department of Microbiology, Vardhman Mahaveer Medical College and Safdarjung Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Background: Rhodotorula spp. are an emergent opportunistic pathogen, particularly in immunocompromised individuals. Materials and Methods: The aim of the study was to review reported cases of Rhodotorula infection over a period of 9 years to determine epidemiology, risk factors, treatment and outcome. Results: The Rhodotorula spp. were isolated from cerebrospinal fluid (9) and blood (5). The most common pre-disposing factors were prolonged hospital stay (>1 month) and prolonged usage of broad-spectrum antibiotics (>1 month). All the isolates were identified as R. mucilaginosa by conventional methods. Amphotericin B demonstrated lowest minimum inhibitory concentration (MIC) as compared with other anti-fungal agents (fluconazole, itraconazole and voriconazole). Conclusions: The recognition of unusual yeasts as an agent of life-threatening infection and their intrinsic resistance increases the burden on the mycology laboratory for complete species identification and to determine minimum inhibitory concentration.
Keywords: Anti-fungal susceptibility, emergent yeast, immunosuppression, Rhodotorula spp.
|How to cite this article:|
Capoor M R, Aggarwal S, Raghvan C, Gupta D K, Jain A K, Chaudhary R. Clinical and microbiological characteristics of Rhodotorula mucilaginosa infections in a tertiary-Care facility. Indian J Med Microbiol 2014;32:304-9
|How to cite this URL:|
Capoor M R, Aggarwal S, Raghvan C, Gupta D K, Jain A K, Chaudhary R. Clinical and microbiological characteristics of Rhodotorula mucilaginosa infections in a tertiary-Care facility. Indian J Med Microbiol [serial online] 2014 [cited 2020 Oct 23];32:304-9. Available from: https://www.ijmm.org/text.asp?2014/32/3/304/136576
| ~ Introduction|| |
The past few decades have witnessed infections due to yeasts as a common and significant cause of morbidity and mortality in immunocompromised patients. Previously fungal infections were caused by yeasts like Candida spp. Cryptococcus neoformans and dimorphic fungi. However, currently saprophytic yeasts like Trichosporon spp., Malassezia spp., Geotrichum candidum and Rhodotorula spp. are emerging pathogens. 
Rhodotorula is an ubiquotous environmental and air borne saprophyte, but now it is being increasingly isolated from immunocompromised patients.  Large numbers of studies have described Rhodotorula spp. as a cause of human mycoses,
there are few reviews in the literature citing the epidemiology, risk factors and outcomes related to Rhodotorula infection. ,, The main purpose of this study was to review all cases of human Rhodotorula infection in a tertiary-care hospital and to describe the underlying condition, risk factors, treatment and outcome of these cases.
| ~ Materials and Methods|| |
The current study was done in a tertiary-care hospital from January 2002 to December 2010. A total of 14 cases of Rhodotorula species were taken up for study. These were unrelated cases, isolated over a period of 9 years, not on same floor or ward or treating physician. Epidemiological data included age, gender, risk factors, underlying conditions, treatment and outcome. The risk factors accessed were broad-spectrum antibiotics (>1 month) (third generation cephalosporin, combination beta-lactamase inhibitor, carbepenems), neutropenia, prolonged hospital stay (>1 month) and central venous catheter (CVC). These yeasts were isolated from cerebrospinal fluid (CSF) and blood samples of different patients from a previously sterile site.
- Isolation of Rhodotorula spp. fulfilling the criteria for a blood stream infection was defined as one culture of Rhodotorula spp. either from the peripheral blood or the CVC tip as per Centre for Disease Control (CDC) 
- Fungal meningitis caused by Rhodotorula spp. was defined by one and more isolation of Rhodotorula spp. in culture (on multiple media) with pleocytosis and clinical signs of meningitis. 
These isolates were identified on the basis of Gram's stain, colony characteristics on Mac-conkey agar, blood agar chocolate agar and Sabouraud's dextrose agar (SDA), cornmeal agar (CMA), urease test, carbon and nitrogen assimilation pattern and API 20 C yeast identification strips (bioMerieux, France). [Figure 1] depicts growth of Rhodotorula spp.: orange-red carotenoid pigment producing mucoid colonies on SDA. Representative isolates (two) of Rhodotorula mucilaginosa were randomly selected and reconfirmed by phenotypic methods at National Culture Collection of Medically important fungi at the Postgraduate Institute of Medical Education and Research, Chandigarh, India.
|Figure 1: Depicts growth of Rhodotorula spp.: Orange-red carotenoid pigment producing mucoid colonies on SDA|
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Anti-fungal susceptibility was done on Roswell Park Memorial Institute (RPMI) 1640 media by using E-strips and broth microdilution methods for amphotericin B, itraconazole, fluconazole and voriconazole. Caspofungin was not included in the study due to non-availability of the drug. As Rhodotorula species, such as Cryptococcus spp., are heterobasidiomycetes and thus are reliably tested by Clinical Laboratory Standard Institute (CLSI) guidelines 2002  and 2009. 
Risk factors analysis model of infection was performed.
| ~ Results|| |
A total of 14 Rhodotorula spp. were isolated from 2967 suspected invasive fungal infection cases received at the Microbiology Department over a period of 9 years [2002-2010, [Table 1]]. Nine cases were identified from neurology and five from the haematology ward. The clinical presentations in these patients were chronic meningitis (9) and fungaemia (5) and these were isolated from CSF and blood, respectively. All Rhodotorula were repeatedly isolated (>2 samples).
[Table 2] shows clinico-investigative profile of 14 cases of Rhodotorula infection included in the study. Thirteen isolates were identified in adults and the remaining single isolate was from a six-year-old patient. Eight (57.14%) cases of Rhodotorula infection occurred in males and six (42.85%) in females. All patients were on broad-spectrum antibiotics (third generation cephalosporins, combination beta-lactams, penems) >1 month and more than 1 month stay in the hospital. Nine (64.28%) patients had immunosuppression due to prolonged use of steroids, five (35.71%) were on haematological malignancy-related chemotherapy, neutropenia and prior prophylactic fluconazole therapy. Two (13.34%) cases presented with hydrocephalous with shunt and one (7.14%) patient had CVC. None of the patients had received total parenteral nutrition or had history of human immunodeficiency virus (HIV) seropositivity. Only three (21.4%) cases were successfully treated with amphotericin B, seven (50%) cases were lost to follow up and four (28.57%) cases left against medical advice. All the isolates were sensitive to amphotericin B with range of 0.25-1 μg/ml and 13 (92.85%) isolates were resistant to fluconazole, itraconazole and voriconazole. The overall patient management included anti-fungal treatment, removal of CVC (one) and correction of the underlying condition (five;35.71%). In all three treated cases, amphotericin B was given for 2 weeks till the last culture was negative. In case no. four and five durations of treatment was 6 weeks and in case no. 14, it was 21 days.
|Table 2: Clinico - investigative profile of 14 cases of Rhodotorula infection included in the study |
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Risk factors analysis model of infection was performed. Except presence of Acute myeloid leukaemia (AML) with neutropenia all other risk factors are found to be non-significantly associated with outcome [Figure 2]. Furthermore, Use of broad-spectrum antibiotics (third generation cephalosporins, combination beta-lactams, penems) >1 month and more than 1 month stay in the hospital were seen in all patients with Rhodotorula infection. Mortality by Kaplan curve was also assessed [Figure 3]. It revealed that probability of cumulative survival was decreasing in the treatment group.
|Figure 3: Kaplan-Mier curve shows that probability of cumulative survival is decreasing in the treatment group|
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| ~ Discussion|| |
Rhodotorula spp. is ubiquitous in distribution. It is found in soil, air, lakes, ocean, water and dairy products. Furthermore, it is non-pathogenic coloniser of plants, humans and other mammals (like shrimps). In this study Rhodotorula spp. caused systemic infections like chronic meningitis in nine (64.28%) patients, fungaemia with haematological malignancy and neutropenia in five (35.71%) cases. Recently it has become an emergent pathogen, causing both local and systemic opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS), cancer, leukaemia, etc.  Documented Rhodotorula infections include fungaemia (79%), endocarditis, eye infections (7.03%) (keratitis, endopthalmitis, dacryocystitis, corneal infections), ventriculitis, meningitis (3.9%), peritonitis, etc., Rare cases include hydrosalphingitis, orthopaedic prosthesis infection, disseminated infection with bone-marrow involvement. , But few epidemiological studies have described Rhodotorula as the aetiological agent in 0.5-2.3% cases of fungaemia. ,, In this study from 2002 to 2010, 14 isolates of Rhodotorula were isolated. In first 3 years, no Rhodotorula spp. were isolated from samples. After this, an increase in number of Rhodotorula has been reported. This could be attributed to increase in number of immunosuppressed patients, leading to increase in the samples for invasive fungal disease, thereby leading to escalated isolations of such yeasts. Since the past two decades, there is increase in the rate of Rhodotorula infections due to introduction of new modalities of treatment related to critical care and transplantation involving extensive CVC, total parenteral nutrition, broad spectrum antibiotics and cytotoxic drug usage.  The current study depicted high isolation of Rhodotorula spp. from central nervous system infection as compared with other sites. A prior study showed concordant results as compared with this study, the incidence of fungal infections of central nervous system has shown a steep rise, largely due to the advent of AIDS and the wide spread use of broad spectrum antibiotics, steroids, immunosuppressive drugs and advanced technology.  There were nine cases of Rhodotorula infections in chronic meningitis patients, but only two had shunts; therefore these were considered as nosocomial or related procedures.
In this study secondary immunosuppression in Rhodotorula infections was due to prolong usage of broad spectrum antibiotics (100%), prolong hospital stay (100%), steroids nine (64.28%) prior prophylatical fluconazole therapy five (35.71%), chemotherapy five (35.71%), neutropenia five (35.71%), hydrocephalous with shunt two (14.28%) and CVC one (7.14%). However, the incidence of these risk factors in other studies ranges from: CVC (62.5-88%), prolonged usage of broad spectrum antibiotics (38-55%), neutropenia (13-40%), and immunosuppressive therapy (10-43%). ,, Similarly, other prior study also observed several risk factors (>/=3) simultaneously in one patient.  The incidence of CVC as risk factor is low in this study because no patient was admitted in intensive care unit. The incidence of risk factor of prolonged use of antibiotics and hospital stay is high as the isolation of Rhodotorula spp. was from patients of chronic meningitis who were on antibiotics and one patient also had a history of tuberculosis (case no. 7) who was on anti-tubercular treatment. The incidence of risk factor of secondary immunosuppression due to neutropenia and immunosuppressive drugs (steroids, chemotherapy drugs) were similar to other studies. AIDS and parenteral nutrition are associated with Rhodotorula infections but they were uncommon in this study. Other unusual conditions associated with fungaemia documented in literature are bone marrow transplant, abdominal surgery, cirrhosis, autoimmune disorder, burns, diabetes mellitus and chronic renal failure. ,,
It may be speculated that the use of broad spectrum antibiotics and exposure to cytotoxic agents probably contributed to the increase in gastroinestinal colonisation and subsequent breech of the intestinal mucosa. It is documented that Rhodotorula spp. can damage gastrointestinal tract. But the studies investigating the true role of gastrointestinal tract as a source of Rhodotorula spp. are few. 
Several previous reports have documented that the presence of CVC as a major risk factor for Rhodotorula fungaemia. This is attributed to skin colonisation or gastrointestinal colonisation of catheter or wide spread distribution of yeast in the environment (i.e. tap water), thus causing infections in the immunosuppressed patient.  The increase of catheter-related Rhodotorula fungaemia is attributed to the increase in aggressive modalities of treatment, which include intensive stay, use of CVC, parenteral nutrition, broad-spectrum antibiotics, organ transplant
and increase in number of AIDS cases. All the more, immunosuppression is very common underlying factor in patients with catheter-related Rhodotorula fungaemia, as was seen in this study the catheter-related Rhodotorula fungaemia patient had neutropenia. Nonetheless, other conditions associated with catheter-related Rhodotorula fungaemia such as abdominal surgery, cirrhosis, autoimmune and burns were not seen in this case series. 
Isolation of Rhodotorula spp. from CSF and blood is of great significance when contamination has been ruled out by repeated isolation from the patient's samples and by growth of Rhodotorula spp. on multiple
Rhodotorula is a heterogeneous group of yeast with 50 different species and different anti-fungal suspectibility.  Therefore, appropriate identification of species is necessary for proper treatment, epidemiological surveys and outbreak management. In this study all the isolation were identified as R. mucilaginosa. This is similar to prior studies that documents R. mucilaginosa as a predominant species of Rhodotorula.,,, Other two common species are R. glutinis and R. minuta.
There is a pertinent data regarding the in vitro susceptibility testing of Rhodotorula species by using CLSI guidelines. In this study, isolates were susceptible to amphotericin B with lowest MIC range of 0.25-1 μg/ml, resistant to fluconazole (MIC range 32-256 μg/ml) itraconazole (MIC range 32-256 μg/ml) and voriconazole (MIC range 0.25-32 μg/ml). Similarly, other studies also reported low MICs to amphotericin B (MIC 0.25-1 μg/ml) and flucytosine (MIC 0.0125-0.25) and low MIC to echinocandins (MIC 0.25-1 μg/ml).  The repeatedly high MIC of fluconazole against Rhodotorula might be due to the presence of intrinsic resistance pattern. ,, Echinocandins like caspofungin and micafungin showed high MIC to Rhodotorula species than to other heterobasidiomycetous yeast.  However, newer anti-fungal agents like ravuconazole and posaconazole showed low MIC in vitro and may appear promising, but there is no clinical experience with these drugs. 
Amphotericin B is the drug of choice in Rhodotorula infection in immunocompromised patients. However, in the immunocompetent patients, this infection can be treated successfully by recovery from underlying conditions and catheter removal. As Rhodotorula infection has low virulence in immunocompetent patients and have good prognosis and therefore require less intensive approach. 
In this study, the duration of treatment ranged from 3 to 6 weeks for successful treatment with amphotericin B. Similarly, one study also documented similar duration of treatment (2-5 weeks).  As per Infectious Disease Society of America (IDSA) 2009, the recommended treatment of candidemia is for 6-8 weeks. 
Several publications suggested overall mortality rate of 12.6-15% due to Rhodotorula infection. , However, in this study the mortality rate could not be assessed as majority of the patients left the hospital without medical advice or were lost to follow up.
| ~ Summary|| |
recognition of unusual yeasts as an agent of life-threatening infection and their intrinsic resistance increases the burden on the mycology laboratory for complete species identification and to determine minimum inhibitory concentration. Furthermore, lack of standardisation and paucity of cases hamper treatment recommendations. Nonetheless, more epidemiological studies are warranted to know the anti-fungal susceptibility to newer anti-fungal and strategies to prevent infection with Rhodotorula spp.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
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